Breast Pathology Lecture - 2013

1. Breast Pathology Lecture - 2013 Knowledge is a burden, If it robs you of innocence, If it makes you feel you are special, If it gives you an idea you are wise, If it is not integrated into life, If it does not bring you joy, If it does not set you free. Sri Sri Ravi Shankar, Humanitarian and founder of the Art of Living Foundation, India.

2. CPC 4.5 – 42y Woman, sore R. breast. Mrs JM is a 45y old woman, primary school teacher, living in Weipa.             “odd change in my left breast when I was showering last week” Duration. Noticed it 8 days ago What? “My left breast feels a bit thicker – points to upper outer quad* Pain No, Nipple discharge: No, Trauma to breast: No Menstrual cycle: regular, Mastalgia: not usually LMP: about 4/52 ago; K due now. Age of menarche: 13 years*, Parity: none* (failed IVF / infertility*) Appetite, Weight : stable* was on COCP* ages 17yrs – 30 yrs. Cervical smear: Never* Menarche aged 13yrs* Has never had mammogram/breast USS* ‘I check regularly’ * CPC 4.5 – 42y Woman, sore R. breast. Mrs JM is a 45y old woman, primary school teacher, living in Weipa.             “odd change in my left breast when I was showering last week” Duration. Noticed it 8 days ago What? “My left breast feels a bit thicker – points to upper outer quad* Pain No, Nipple discharge: No, Trauma to breast: No Menstrual cycle: regular, Mastalgia: not usually LMP: about 4/52 ago; K due now. Age of menarche: 13 years*, Parity: none* (failed IVF / infertility*) Appetite, Weight : stable* was on COCP* ages 17yrs – 30 yrs. Cervical smear: Never* Menarche aged 13yrs* Has never had mammogram/breast USS* ‘I check regularly’ *

3. CPC 4.5- Examination Key .. ? Fibrocystic o R breast NAD, L breast firm thickening ? upper Tumor outer axillary tail ?; no discrete mass ? no skin Cancer tethering ? / changes; no nipple inversion ?; no areola changes ?, no axillary or supracla. LN. No Cancer Paget’s nipple discharge(blood/pus) ? Cancer  What Differentials: Papilloma  Benign proliferations, Breast malignancy Duct ectasia  What further investigations?  Mammogram, FNAB, CT Scan, PET Scan, Biopsy + immunochemistry (HER2) ? Labs: ER PR HER2 BRC CPC 4.5- Examination Key .. ? Fibrocystic o R breast NAD, L breast firm thickening ? upper Tumor outer axillary tail ?; no discrete mass ? no skin Cancer tethering ? / changes; no nipple inversion ?; no areola changes ?, no axillary or supracla. LN. No Cancer Paget’s nipple discharge(blood/pus) ? Cancer  What Differentials: Papilloma  Benign proliferations, Breast malignancy Duct ectasia  What further investigations?  Mammogram, FNAB, CT Scan, PET Scan, Biopsy + immunochemistry (HER2) ? Labs: ER PR HER2 BRC

4. CPC 4.5- Examination      Mammogram – solid* non mobile* irregular* mass lying at the 10 o’clock position of the L breast. Mass has prominent radiating spicules*; 2 x small calcifications* within the mass. Overall mass 1x 1.5x 1cm. US guided FNAB: High grade infiltrating ductal carcinoma ? CT scan: no sign metastatic disease in liver or lung Bone scan: no sign of metastases. Immunochemistry : ER: ++ PR: neg HER2: +++.. ? ? ? (? Sub types, Luminal B) CPC 4.5- Examination      Mammogram – solid* non mobile* irregular* mass lying at the 10 o’clock position of the L breast. Mass has prominent radiating spicules*; 2 x small calcifications* within the mass. Overall mass 1x 1.5x 1cm. US guided FNAB: High grade infiltrating ductal carcinoma ? CT scan: no sign metastatic disease in liver or lung Bone scan: no sign of metastases. Immunochemistry : ER: ++ PR: neg HER2: +++.. ? ? ? (? Sub types, Luminal B)

5. CPC 4.5 – 42y Woman, sore R. breast. 2013 Term 4 CPC 5 Title: Breast Cancer System: Breast Aim: Clinical, Pathology & population study of patients breast disease 1. Demonstrate competency in history taking & the clinical examination of patients with breast disease. 2. Describe the first line investigation and management of patients with breast disease or symptoms. Learning outcomes The student will be 3. Describe the Pathophysiology of breast disease (benign and malignant) able to 4. Outline the basic sciences relating to function of the breasts. 5. Describe the Epidemiology and aetiology of breast disease in Australia and world wide. 6. Illustrate the advantages and disadvantages of the breast screening program in Australia CPC 4.5 – 42y Woman, sore R. breast. 2013 Term 4 CPC 5 Title: Breast Cancer System: Breast Aim: Clinical, Pathology & population study of patients breast disease 1. Demonstrate competency in history taking & the clinical examination of patients with breast disease. 2. Describe the first line investigation and management of patients with breast disease or symptoms. Learning outcomes The student will be 3. Describe the Pathophysiology of breast disease (benign and malignant) able to 4. Outline the basic sciences relating to function of the breasts. 5. Describe the Epidemiology and aetiology of breast disease in Australia and world wide. 6. Illustrate the advantages and disadvantages of the breast screening program in Australia

6. CPC 4.5- Core Learning Issues Pathology Major CLI: • • • • • • Pathology of Breast – overview, classification & common dis.. Breast Lumps - Differential diagnosis. Trauma, infections & Inflam. – Mastitis, fat necrosis, abscess. Hyperplasia – Fibrocystic disease Tumours – Benign – Fibroadenoma, giant fibroadenoma. Breast cancer – etiology, pathogenesis, morphology & complications, Laboratory diagnosis, including markers. Pathology Minor CLI: • • • • Duct ectasia, Breast Cysts. Paget’s disease. Gynecomastia & male breast disorders. CPC 4.5- Core Learning Issues Pathology Major CLI: • • • • • • Pathology of Breast – overview, classification & common dis.. Breast Lumps - Differential diagnosis. Trauma, infections & Inflam. – Mastitis, fat necrosis, abscess. Hyperplasia – Fibrocystic disease Tumours – Benign – Fibroadenoma, giant fibroadenoma. Breast cancer – etiology, pathogenesis, morphology & complications, Laboratory diagnosis, including markers. Pathology Minor CLI: • • • • Duct ectasia, Breast Cysts. Paget’s disease. Gynecomastia & male breast disorders.

7. Case studies:        22year female, noticed small mobile round lump in her right breast, lower inner quadrant. 39year female, multiple small lumps, irregular, firm, tender more during mid cycle. 41year female, two left axillary LN, no pain, no breast mass. mild loss of weight. 34year female, diffuse firm left breast. FNAC reports abnormal cells. No LN. 39year female, painful lump, chronic pus discharge from nipple. 71year old female. Rough, red scaling pruritic patch on left nipple and areola. 26y nurse, right breast lump 5m, firm irregular, 6cm firm, fixed lump. • Fibroadenoma • Fibrocystic dis • Ca breast. • DCIS • Duct ectasia • Paget’s dis • BRCA Ca. Case studies:        22year female, noticed small mobile round lump in her right breast, lower inner quadrant. 39year female, multiple small lumps, irregular, firm, tender more during mid cycle. 41year female, two left axillary LN, no pain, no breast mass. mild loss of weight. 34year female, diffuse firm left breast. FNAC reports abnormal cells. No LN. 39year female, painful lump, chronic pus discharge from nipple. 71year old female. Rough, red scaling pruritic patch on left nipple and areola. 26y nurse, right breast lump 5m, firm irregular, 6cm firm, fixed lump. • Fibroadenoma • Fibrocystic dis • Ca breast. • DCIS • Duct ectasia • Paget’s dis • BRCA Ca.

8. Self assessment: Clinical features of benign, malignant & reactive…  Breast cancer screening guidelines.  Hyperplasia / tumour features.  Familial vs Non familial breast Ca features.  Screening Mammogram – policy, procedure & interpretation.  Fibrocystic disease, fibroadenoma & cancer.  Breast cancer common types & features (gross, microscopy, complications etc.)  Duct carcinoma, lobular carcinoma, other types.  BRCA testing in familial breast ca.  Self assessment: Clinical features of benign, malignant & reactive…  Breast cancer screening guidelines.  Hyperplasia / tumour features.  Familial vs Non familial breast Ca features.  Screening Mammogram – policy, procedure & interpretation.  Fibrocystic disease, fibroadenoma & cancer.  Breast cancer common types & features (gross, microscopy, complications etc.)  Duct carcinoma, lobular carcinoma, other types.  BRCA testing in familial breast ca. 

9. “Strength does not come from winning, Struggles & Hardship develop strength. - - Arnold Schwarzenegger Bodybuilder, Actor & Leader. “Strength does not come from winning, Struggles & Hardship develop strength. - - Arnold Schwarzenegger Bodybuilder, Actor & Leader.

10. . Pathology of Breast Dr. Venkatesh M. Shashidhar Associate Prof. & Head of Pathology

11. . CPC- 44 – Core learning Issues  Major CLI:      Pathology of breast diseases – over view Congenital, Inflammatory & Neoplastic disorders. Breast Lumps – Hyperplasia – Fibrocystic disease. Benign neoplasms: Fibroadenoma, Duct papilloma & Breast cancer – Ductal Carcinoma & DCIS. Minor CLI:      Cong: Hypertrophy, atrophy, accessory, supernumerary.. Mastitis (acute/chronic), Breast trauma, fat necrosis. Phyllodes tumor, other carcinoma (Lobular etc) Duct ectasia. Paget’s disease.

12. . Introduction: Anatomy Modified sweat glands. Lobes and lobules of gland in fat tissue stroma. Ducts emerge from acini of glands Smaller ducts join to form lactiferous ducts Lactiferous ducts merge just beneath the nipple to form a lactiferous sinus. Then individually open on nipple

13. . Anatomy T4 level

14. . Breast Physiology: Male Female

15. . Normal Breast – glands & stroma Dense stroma Loose stroma Acinus

16. . Normal Breast – glands & stroma Loose stroma Acinus Dense stroma

17. . Breast – Acini (SEM)

18. . Age changes in breast: Puberty Fibrous  Adult (Lactating) Fibro-Fatty  Menopause Fat

19. . Disorders of Breast:  Congenital    Inflammatory      Acute: lactational* / Chronic Mastitis Trauma – Traumatic Fat necrosis Duct ectasia – chronic, discharge, sinus, Galactocele Proliferative Conditions    Aplasia : turners / Juvenile hypertrophy Accessory/ectopic breasts – along milk line Fibrocystic disease – common cause of lumps Cysts, Adenosis, Metaplasia & mixed. Neoplastic   Benign – Fibroadenoma, duct papilloma Malignant – Ductal Carcinoma & DCIS – several types.

20. . Disorders of Breast:

21. . Gynecomastia:        Breast enlargement in men. Estrogen excess – Klinefelter’s, Hyperthyroidism, pitu itary & adrenal tumors, testicular failure, hormonal. Liver failure, cirrhosis Lung, Testicular Cancer diethylstilbestrol therapy for prostatic carcinoma. Drugs (Spironolactone, H2 antagonists, Neuroactive agents). Microscopy – only duct & stromal hyperplasia. (no acini)

22. . Acute Mastitis:  Acute Mastitis:   Non Lactational (central, periductal, rare) Lactational (periphery, common)      First few weeks after delivery. Crack in the nipple – entry point. Staph. aureus, Strep. pyogenes. Localized inflammation, Swelling erythema & pus. Chronic Mastitis:    Granulomatous (TB, Fungal, Silicone etc.) Traumatic fat necrosis: Chronic granuloma, foam macrophages, radial scar – dd Ca. Diabetic mastopathy: DM1, rubbery lymphocytic.

23. . Duct Ectasia: Mimics Ca.     >50y, multiparous. Periareolar mass with white, cheesy nipple discharge. Duct obstruction/destruction, inflammation, dilation, fibrosis with fat globules & foamy macrophages in lumen. Recurrent abscess / fistula. Scarring with nipple inversion may mimic Ca.

24. . Lump in Breast: Diagnosis & Features Clinical presentation <25 years 25-35 years 35-55 years >55 years Mobile lump (single) Fibroadenoma Fibroadenoma Fibroadenoma Phyllodes tumour Phyllodes tumour ill-defined lump/s or lumpy areas – cyclic pain. Uncommon Fibrocystic change Uncommon Firm lump tethering (fixed) Uncommon Fibrocystic change Sclerosing adenosis Carcinoma* Carcinoma Carcinoma Fat necrosis Nipple discharge Clear/pus Uncommon Uncommon Duct ectasia Duct ectasia Bloody Uncommon Uncommon Duct papilloma Duct papilloma In situ carcinoma Paget's disease In situ carcinoma Paget's disease Nipple adenoma Nipple adenoma Nipple ulceration, eczema Nipple adenoma Nipple adenoma

25. . Fibrocystic Disease/change:      Pathology: Harmone induced acinar hyperplasia. Oestrogens* Clinical: Commonest (40%) cause of lumps in 20-40y. Irregular induration/ lumps. Cyclic pain/discomfort. Gross: Grey white scar tissue with cysts. Micro: Fibrosis, cysts, hyperplastic glands. Pathogenesis: Hyperplasia of glands and stroma  DCIS  Carcinoma.

26. . Fibrocystic Disease

27. . FibroCystic Disease: types Non prol. / low grade Prol. / High grade A. Simple Fibrocystic change. B. Lobular hyperplaisa without atypica (adenosis) C,D - Ductal hyperplasia without atypia (E. with atypia - cribriform) F. Lobular hyperplasia.

28. . FCD: Cysts, Fibrosis & Proliferation

29. . FCD + Ductal Hyperplasia* Hyperplasia may progress to DCIS (Duct Carcinoma In-Situ). Progress to duct carcinoma.

30. . FCD: Ep. Hyperpl. - Sclerosing Adenosis* Small duct proliferation. Clinical & biopsy mimics carcinoma.

31. . Fibrocystic Disease-Blue dome cyst When single large cyst - blue

32. . Education must instill the fundamental human values; it must broaden the vision to include the entire world and all mankind. Education must equip man to live happily. -- Satya Sai Baba

33. . Breast Neoplasms:  Benign: (round, smooth, soft, mobile)  Fibroadenoma  Duct Papilloma  Others – rare.  Malignant: (irregular, rough, hard, fixed)  Ductal carcinoma – classic.  Lobular carcinoma  Others - rare Fibrocystic Disease (Not a neoplasm)

34. . Fibroadenoma Types Solitary Few (< 5 / breast ) Multiple (> 5 / breast ) Giant (> 4 / 5 cms) & Juvenile Low grade Benign Natural history Majority remain small & static 50% involute spontaneously No future risk of malignancy High grade

35. . Fibroadenoma Pathology: Benign tumor of acini tissue (gland & stroma) Clinical: Well demarcated, mobile, round/nod (mouse) Gross: Capsulated, firm grey, nodular tumour, cysts+/-. Micro: Compressed slit like ducts/glands in cellular stroma.

36. . Mammogram - Benign

37. . Fibroadenoma Note: well demarcated, capsulated, nodular tumour

38. . Fibroadenoma

39. . Fibroadenoma In P P In P C = capsule; In = intracanicular pattern; P = pericanicular pattern

40. . Fibroadenoma Summary:  Small discrete mobile.  Stromal neoplasm with reactive glands.  No malignant potential.  Regress / calcify in menopause.  Increase in pregnancy.

41. . Giant Fibroadenoma     Pathology: Benign(young) to malignant(adult) tumor of acinii. Clinical: young (Low grade) /adult (high grade)*, unilateral macromastia, recurrent, metastasis 15%. Gross: Large 10-15cm . Giant. With linear “leaf-like” clefts and slits – Giant/Juvenile in young - Phyllodes tumor in adult. Micro: Both stroma & glands are hypercellular & pleomorphic. glands show branching..

42. . Fibroadenoma Flat slit glands, fibrous stroma, Benign. – Giant Fibroadenoma Branching leaf like glands, Cellular stroma Benign 85%  malignant 15%.

43. . Intraductal papilloma     Clinical: Middle age, Bloody discharge, sub areolar lump. Duct wall Gross: Solitary, Intra-ductal papillary Proliferation. Micro/Path: Benign papillary proliferation of lactiferous duct epithelium. Stalk & papillae Prognosis: recurrent, but no risk of malignancy. (rare)

44. . Education has two important characteristics. One is learning of a subject & skill. The other is the personality to apply this knowledge to the benefit of community. --Baba One without the other is either useless or dangerous…. ! Knowledge, Skill & Attitude * JCU graduate attributes..

45. . Breast Carcinoma – Aus. stat.  The most common cancer among Australian women (also in aboriginals). (20%)  UK 1 in 10 women, 1 in 8 in US, 1 in 9 Aus.  One in nine women before the age of 85.  28% of all cancer diagnoses in 2006.  Increased from 5,289 in 1982 to 12,614 in 2006  Commonest cause of death in young < 55y  Rare before age 30. (30-50 genetic, >50 sporadic)  Much less incidence in Asia, Japan.  Majority of cancers arise in the ducts.  Survival is improving with therapy. (96% 5y – 2006)

46. . Etiology of Breast Carcinoma: • HER2/NEU • RAS & MYC • BRC A1, A2. Environment Hormone • Family history – First degree relative. • Premenopausal & bilateral. • Early menarche/Late menopause. • • • • Genetics • Estrogen therapy. • Alcohol, Smoking. • High fat diet, Obesity. Overexposure to oestrogens and underexposure to progesterone No definite relationship to oral contraceptives Some tumours contain hormone receptors and respond to hormone manipulation No good evidence for viral involvement

47. . Pathogenesis of Breast Cancer. Duct Ca. in-Situ DCIS Hyperplasia  Dysplasia  DCIS  Carcinoma Fibrocystic change  Cancer

48. . Pathogenesis:

49. . Ductal Carcinoma in Situ (DCIS)  Dysplastic cells filling ducts with Ca+, no invasion. Pre-cancer state.  Increasing incidence of DCIS due to mammographic screening. (diffuse irregular firm/lumpy areas)  Spreads throughout ductal system to produce extensive lesions.  Many types: solid cribriform, papillary, and micropapilary, comedo type or mixed pattern. (dysplasia: low – high grade)  Progress to invasive carcinoma.

50. . Ductal Carcinoma in Situ, DCIS